SC5A8_HUMAN
ID SC5A8_HUMAN Reviewed; 610 AA.
AC Q8N695; Q2TB99; Q7Z2H9;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Sodium-coupled monocarboxylate transporter 1;
DE AltName: Full=Apical iodide transporter;
DE AltName: Full=Electrogenic sodium monocarboxylate cotransporter;
DE AltName: Full=Sodium iodide-related cotransporter;
DE AltName: Full=Solute carrier family 5 member 8;
GN Name=SLC5A8 {ECO:0000312|EMBL:AAP46193.1};
GN Synonyms=AIT {ECO:0000312|EMBL:AAL88746.1},
GN SMCT {ECO:0000303|PubMed:14966140, ECO:0000303|PubMed:15090606},
GN SMCT1 {ECO:0000303|PubMed:16729224};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL88746.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INHIBITION.
RC TISSUE=Kidney {ECO:0000312|EMBL:AAL88746.1};
RX PubMed=12107270; DOI=10.1210/jcem.87.7.8797;
RA Rodriguez A.-M., Perron B., Lacroix L., Caillou B., Leblanc G.,
RA Schlumberger M., Bidart J.-M., Pourcher T.;
RT "Identification and characterization of a putative human iodide transporter
RT located at the apical membrane of thyrocytes.";
RL J. Clin. Endocrinol. Metab. 87:3500-3503(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAP46193.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT ILE-193, FUNCTION,
RP INDUCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Colon {ECO:0000269|PubMed:12829793};
RX PubMed=12829793; DOI=10.1073/pnas.1430846100;
RA Li H., Myeroff L., Smiraglia D., Romero M.F., Pretlow T.P., Kasturi L.,
RA Lutterbaugh J., Rerko R.M., Casey G., Issa J.-P., Willis J., Willson J.K.,
RA Plass C., Markowitz S.D.;
RT "SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by
RT methylation in human colon aberrant crypt foci and cancers.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8412-8417(2003).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, STOICHIOMETRY,
RP AND VARIANTS ILE-193 AND VAL-251.
RC TISSUE=Intestine {ECO:0000269|PubMed:14966140};
RX PubMed=14966140; DOI=10.1074/jbc.c400059200;
RA Miyauchi S., Gopal E., Fei Y.-J., Ganapathy V.;
RT "Functional identification of SLC5A8, a tumor suppressor down-regulated in
RT colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids.";
RL J. Biol. Chem. 279:13293-13296(2004).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, STOICHIOMETRY,
RP AND INHIBITION.
RC TISSUE=Kidney cortex {ECO:0000269|PubMed:15090606};
RX PubMed=15090606; DOI=10.1113/jphysiol.2004.063859;
RA Coady M.J., Chang M.-H., Charron F.M., Plata C., Wallendorff B., Sah J.F.,
RA Markowitz S.D., Romero M.F., Lapointe J.-Y.;
RT "The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate
RT cotransporter.";
RL J. Physiol. (Lond.) 557:719-731(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6] {ECO:0000312|EMBL:EAW97649.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000312|EMBL:AAI10493.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15001644; DOI=10.1210/jc.2003-030542;
RA Lacroix L., Pourcher T., Magnon C., Bellon N., Talbot M., Intaraphairot T.,
RA Caillou B., Schlumberger M., Bidart J.-M.;
RT "Expression of the apical iodide transporter in human thyroid tissues: a
RT comparison study with other iodide transporters.";
RL J. Clin. Endocrinol. Metab. 89:1423-1428(2004).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15361710; DOI=10.1159/000079145;
RA Ueno M., Toyota M., Akino K., Suzuki H., Kusano M., Satoh A., Mita H.,
RA Sasaki Y., Nojima M., Yanagihara K., Hinoda Y., Tokino T., Imai K.;
RT "Aberrant methylation and histone deacetylation associated with silencing
RT of SLC5A8 in gastric cancer.";
RL Tumor Biol. 25:134-140(2004).
RN [10] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
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 [11] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17178845; DOI=10.1158/0008-5472.can-06-1950;
RA Thangaraju M., Gopal E., Martin P.M., Ananth S., Smith S.B., Prasad P.D.,
RA Sterneck E., Ganapathy V.;
RT "SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition
RT of histone deacetylases.";
RL Cancer Res. 66:11560-11564(2006).
RN [12] {ECO:0000305}
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [13] {ECO:0000305}
RP FUNCTION, AND INHIBITION.
RX PubMed=16729224; DOI=10.1007/s11095-006-0023-1;
RA Itagaki S., Gopal E., Zhuang L., Fei Y.-J., Miyauchi S., Prasad P.D.,
RA Ganapathy V.;
RT "Interaction of ibuprofen and other structurally related NSAIDs with the
RT sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).";
RL Pharm. Res. 23:1209-1216(2006).
RN [14] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18037591; DOI=10.1016/j.cdp.2007.09.002;
RA Park J.Y., Zheng W., Kim D., Cheng J.Q., Kumar N., Ahmad N., Pow-Sang J.;
RT "Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by
RT promoter hypermethylation in prostate tumor.";
RL Cancer Detect. Prev. 31:359-365(2007).
RN [15] {ECO:0000305}
RP FUNCTION, STOICHIOMETRY, 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).
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. Acts as a tumor suppressor, suppressing
CC colony formation in colon cancer, prostate cancer and glioma cell
CC lines. May play a critical role in the entry of L-lactate and ketone
CC bodies into neurons by a process driven by an electrochemical Na(+)
CC gradient and hence contribute to the maintenance of the energy status
CC and function of neurons. {ECO:0000269|PubMed:12107270,
CC ECO:0000269|PubMed:12829793, ECO:0000269|PubMed:14966140,
CC ECO:0000269|PubMed:15090606, ECO:0000269|PubMed:15361710,
CC ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:16729224,
CC ECO:0000269|PubMed:16805814, ECO:0000269|PubMed:17178845,
CC ECO:0000269|PubMed:17245649, ECO:0000269|PubMed:18037591}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1442 uM for beta-D-hydroxybutyate {ECO:0000269|PubMed:16805814};
CC KM=2327 uM for beta-L-hydroxybutyate {ECO:0000269|PubMed:16805814};
CC KM=1088 uM for D-lactate {ECO:0000269|PubMed:16805814};
CC KM=184 uM for L-lactate {ECO:0000269|PubMed:16805814};
CC KM=387 uM for pyruvate {ECO:0000269|PubMed:16805814};
CC KM=213 uM for acetoacetate {ECO:0000269|PubMed:16805814};
CC KM=209 uM for alpha-ketoisocaproate {ECO:0000269|PubMed:16805814};
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:12107270, ECO:0000269|PubMed:15001644,
CC ECO:0000269|PubMed:17245649}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12107270, ECO:0000269|PubMed:15001644,
CC ECO:0000269|PubMed:17245649}. Note=Expressed at the apical membrane of
CC normal tall thyrocytes and of colonic epithelial cells.
CC {ECO:0000269|PubMed:12107270, ECO:0000269|PubMed:15001644,
CC ECO:0000269|PubMed:17245649}.
CC -!- TISSUE SPECIFICITY: Expressed in normal thyroid, localized at the
CC apical pole of thyroid cells facing the colloid lumen, but expression
CC profoundly decreased in thyroid carcinomas. Expressed in normal colon
CC but absent in colon aberrant crypt foci and colon cancers. Present in
CC normal kidney cortex, brain, prostate, gastric mucosa and breast tissue
CC but was significantly down-regulated in primary gliomas, gastric
CC cancer, prostate tumors and breast tumors.
CC {ECO:0000269|PubMed:12107270, ECO:0000269|PubMed:12829793,
CC ECO:0000269|PubMed:14966140, ECO:0000269|PubMed:15001644,
CC ECO:0000269|PubMed:15090606, ECO:0000269|PubMed:15361710,
CC ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:17178845,
CC ECO:0000269|PubMed:17245649, ECO:0000269|PubMed:18037591}.
CC -!- INDUCTION: Down-regulated in some primary cancers; due to aberrant
CC methylation in primary colon cancers, astrocytomas and
CC oligodendrogliomas as well as in cancers of the colon, prostate and
CC gastric regions, and glial cell lines. Expression reactivated on
CC treatment with a demethylating drug, 5-azacytidine.
CC {ECO:0000269|PubMed:12829793, ECO:0000269|PubMed:15361710,
CC ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:18037591}.
CC -!- MISCELLANEOUS: Increase of iodide influx inhibited by addition of
CC perchlorate (NaClO(4)), a competitive inhibitor of iodide uptake
CC catalyzed by sodium iodide symporter (NIS). Cotransport of
CC monocarboxylates and nicotinate strongly inhibited by probenecid,
CC nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen,
CC naproxen) in a Na(+)-dependent manner or by prolonged exposure to
CC external concentrations of monocarboxylates.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000255}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SLC5A8ID44089ch12q23.html";
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DR EMBL; AY081220; AAL88746.1; -; mRNA.
DR EMBL; AF536216; AAP46193.1; -; mRNA.
DR EMBL; AF536217; AAP46194.1; -; Genomic_DNA.
DR EMBL; AC079953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97649.1; -; Genomic_DNA.
DR EMBL; BC110492; AAI10493.1; -; mRNA.
DR CCDS; CCDS9080.1; -.
DR RefSeq; NP_666018.3; NM_145913.3.
DR PDB; 7SL9; EM; 3.50 A; A=1-610.
DR PDBsum; 7SL9; -.
DR AlphaFoldDB; Q8N695; -.
DR SMR; Q8N695; -.
DR BioGRID; 127763; 29.
DR IntAct; Q8N695; 22.
DR STRING; 9606.ENSP00000445340; -.
DR DrugBank; DB01762; Acetoacetic acid.
DR DrugBank; DB00121; Biotin.
DR DrugBank; DB08872; Gabapentin enacarbil.
DR DrugBank; DB08949; Inositol nicotinate.
DR DrugBank; DB00627; Niacin.
DR DrugCentral; Q8N695; -.
DR GuidetoPHARMACOLOGY; 922; -.
DR TCDB; 2.A.21.5.3; the solute:sodium symporter (sss) family.
DR GlyGen; Q8N695; 4 sites, 3 O-linked glycans (3 sites).
DR iPTMnet; Q8N695; -.
DR PhosphoSitePlus; Q8N695; -.
DR BioMuta; SLC5A8; -.
DR DMDM; 296452898; -.
DR jPOST; Q8N695; -.
DR MassIVE; Q8N695; -.
DR PaxDb; Q8N695; -.
DR PeptideAtlas; Q8N695; -.
DR PRIDE; Q8N695; -.
DR ProteomicsDB; 72147; -.
DR Antibodypedia; 51376; 182 antibodies from 24 providers.
DR DNASU; 160728; -.
DR Ensembl; ENST00000536262.3; ENSP00000445340.2; ENSG00000256870.3.
DR Ensembl; ENST00000572861.3; ENSP00000461697.2; ENSG00000262217.3.
DR GeneID; 160728; -.
DR KEGG; hsa:160728; -.
DR MANE-Select; ENST00000536262.3; ENSP00000445340.2; NM_145913.5; NP_666018.3.
DR UCSC; uc001thz.5; human.
DR CTD; 160728; -.
DR DisGeNET; 160728; -.
DR GeneCards; SLC5A8; -.
DR HGNC; HGNC:19119; SLC5A8.
DR HPA; ENSG00000256870; Group enriched (cervix, kidney, thyroid gland).
DR MIM; 608044; gene.
DR neXtProt; NX_Q8N695; -.
DR OpenTargets; ENSG00000256870; -.
DR PharmGKB; PA134989874; -.
DR VEuPathDB; HostDB:ENSG00000256870; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000155166; -.
DR HOGENOM; CLU_018808_11_1_1; -.
DR InParanoid; Q8N695; -.
DR OMA; ILSYKSH; -.
DR OrthoDB; 1180002at2759; -.
DR PhylomeDB; Q8N695; -.
DR TreeFam; TF316728; -.
DR PathwayCommons; Q8N695; -.
DR Reactome; R-HSA-197264; Nicotinamide salvaging.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR SABIO-RK; Q8N695; -.
DR SignaLink; Q8N695; -.
DR SIGNOR; Q8N695; -.
DR BioGRID-ORCS; 160728; 13 hits in 1061 CRISPR screens.
DR ChiTaRS; SLC5A8; human.
DR GeneWiki; SLC5A8; -.
DR GenomeRNAi; 160728; -.
DR Pharos; Q8N695; Tchem.
DR PRO; PR:Q8N695; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8N695; protein.
DR Bgee; ENSG00000256870; Expressed in olfactory segment of nasal mucosa and 49 other tissues.
DR Genevisible; Q8N695; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0140161; F:monocarboxylate:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0005343; F:organic acid:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0022803; F:passive transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015552; F:propionate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0034356; P:NAD biosynthesis via nicotinamide riboside salvage pathway; TAS:Reactome.
DR GO; GO:0015730; P:propanoate transport; IBA:GO_Central.
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 3D-structure; Apoptosis; Cell membrane; Glycoprotein; Ion transport;
KW Membrane; Reference proteome; Sodium; Sodium transport; Symport;
KW Transmembrane; Transmembrane helix; Transport; Tumor suppressor.
FT CHAIN 1..610
FT /note="Sodium-coupled monocarboxylate transporter 1"
FT /id="PRO_0000334499"
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..83
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..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..189
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..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..610
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 585..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 592..610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 485
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 193
FT /note="V -> I (in dbSNP:rs1709189)"
FT /evidence="ECO:0000269|PubMed:12829793,
FT ECO:0000269|PubMed:14966140"
FT /id="VAR_057336"
FT VARIANT 251
FT /note="F -> V (in dbSNP:rs11834933)"
FT /evidence="ECO:0000269|PubMed:14966140"
FT /id="VAR_057337"
FT CONFLICT 490
FT /note="M -> I (in Ref. 1; AAL88746 and 2; AAP46193/
FT AAP46194)"
FT /evidence="ECO:0000305"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 15..33
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 55..65
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 74..81
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 82..87
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 88..101
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:7SL9"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 132..158
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 164..174
FT /evidence="ECO:0007829|PDB:7SL9"
FT TURN 175..180
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 187..211
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 214..223
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 242..257
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 265..268
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 273..304
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 323..330
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 338..368
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 378..385
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 387..402
FT /evidence="ECO:0007829|PDB:7SL9"
FT STRAND 405..410
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 411..418
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 421..432
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 439..462
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 467..470
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 511..515
FT /evidence="ECO:0007829|PDB:7SL9"
FT TURN 516..518
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 526..532
FT /evidence="ECO:0007829|PDB:7SL9"
FT HELIX 534..542
FT /evidence="ECO:0007829|PDB:7SL9"
SQ SEQUENCE 610 AA; 66578 MW; 47FF410B895DB692 CRC64;
MDTPRGIGTF VVWDYVVFAG MLVISAAIGI YYAFAGGGQQ TSKDFLMGGR RMTAVPVALS
LTASFMSAVT VLGTPSEVYR FGAIFSIFAF TYFFVVVISA EVFLPVFYKL GITSTYEYLE
LRFNKCVRLC GTVLFIVQTI LYTGIVIYAP ALALNQVTGF DLWGAVVATG VVCTFYCTLG
GLKAVIWTDV FQVGIMVAGF ASVIIQAVVM QGGISTILND AYDGGRLNFW NFNPNPLQRH
TFWTIIIGGT FTWTSIYGVN QSQVQRYISC KSRFQAKLSL YINLVGLWAI LTCSVFCGLA
LYSRYHDCDP WTAKKVSAPD QLMPYLVLDI LQDYPGLPGL FVACAYSGTL STVSSSINAL
AAVTVEDLIK PYFRSLSERS LSWISQGMSV VYGALCIGMA ALASLMGALL QAALSVFGMV
GGPLMGLFAL GILVPFANSI GALVGLMAGF AISLWVGIGA QIYPPLPERT LPLHLDIQGC
NSTYNETNLM TTTEMPFTTS VFQIYNVQRT PLMDNWYSLS YLYFSTVGTL VTLLVGILVS
LSTGGRKQNL DPRYILTKED FLSNFDIFKK KKHVLSYKSH PVEDGGTDNP AFNHIELNSD
QSGKSNGTRL
