MOT1_MOUSE
ID MOT1_MOUSE Reviewed; 493 AA.
AC P53986;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Monocarboxylate transporter 1;
DE Short=MCT 1;
DE AltName: Full=Solute carrier family 16 member 1;
GN Name=Slc16a1; Synonyms=Mct1;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8603082; DOI=10.1016/0005-2736(95)00254-5;
RA Carpenter L., Poole R.C., Halestrap A.P.;
RT "Cloning and sequencing of the monocarboxylate transporter from mouse
RT Ehrlich Lettre tumour cell confirms its identity as MCT1 and demonstrates
RT that glycosylation is not required for MCT1 function.";
RL Biochim. Biophys. Acta 1279:157-163(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129; TISSUE=Kidney;
RX PubMed=9725820; DOI=10.1152/ajpendo.1998.275.3.e516;
RA Koehler-Stec E.M., Simpson I.A., Vannucci S.J., Landschulz K.T.,
RA Landschulz W.H.;
RT "Monocarboxylate transporter expression in mouse brain.";
RL Am. J. Physiol. 275:E516-E524(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-224 AND SER-491, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213; SER-230; SER-461;
RP THR-462; SER-477 AND SER-491, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; SER-213; SER-220;
RP SER-230; SER-477; SER-482; SER-483 AND SER-491, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22522610; DOI=10.2337/db11-1531;
RA Pullen T.J., Sylow L., Sun G., Halestrap A.P., Richter E.A., Rutter G.A.;
RT "Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse
RT pancreatic beta-cells leads to relative hyperinsulinism during exercise.";
RL Diabetes 61:1719-1725(2012).
RN [12]
RP REVIEW.
RX PubMed=22162139; DOI=10.1002/iub.572;
RA Halestrap A.P., Wilson M.C.;
RT "The monocarboxylate transporter family--role and regulation.";
RL IUBMB Life 64:109-119(2012).
RN [13]
RP INTERACTION WITH BSG, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=21792931; DOI=10.1002/jcp.22949;
RA Mannowetz N., Wandernoth P., Wennemuth G.;
RT "Basigin interacts with both MCT1 and MCT2 in murine spermatozoa.";
RL J. Cell. Physiol. 227:2154-2162(2012).
RN [14]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24367518; DOI=10.1371/journal.pone.0082505;
RA Lengacher S., Nehiri-Sitayeb T., Steiner N., Carneiro L., Favrod C.,
RA Preitner F., Thorens B., Stehle J.C., Dix L., Pralong F., Magistretti P.J.,
RA Pellerin L.;
RT "Resistance to diet-induced obesity and associated metabolic perturbations
RT in haploinsufficient monocarboxylate transporter 1 mice.";
RL PLoS ONE 8:E82505-E82505(2013).
CC -!- FUNCTION: Proton-coupled monocarboxylate transporter. Catalyzes the
CC rapid transport across the plasma membrane of many monocarboxylates
CC such as lactate, pyruvate, branched-chain oxo acids derived from
CC leucine, valine and isoleucine, and the ketone bodies acetoacetate,
CC beta-hydroxybutyrate and acetate. Depending on the tissue and on
CC cicumstances, mediates the import or export of lactic acid and ketone
CC bodies. Required for normal nutrient assimilation, increase of white
CC adipose tissue and body weight gain when on a high-fat diet. Plays a
CC role in cellular responses to a high-fat diet by modulating the
CC cellular levels of lactate and pyruvate, small molecules that
CC contribute to the regulation of central metabolic pathways and insulin
CC secretion, with concomitant effects on plasma insulin levels and blood
CC glucose homeostasis. {ECO:0000269|PubMed:22522610,
CC ECO:0000269|PubMed:24367518}.
CC -!- SUBUNIT: Interacts with isoform 2 of BSG; interaction mediates SLC16A1
CC targeting to the plasma membrane (PubMed:21792931). Interacts with EMB;
CC interaction mediates SLC16A1 targeting to the plasma membrane (By
CC similarity). {ECO:0000250|UniProtKB:P53987,
CC ECO:0000269|PubMed:21792931}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21792931,
CC ECO:0000269|PubMed:8603082}; Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Detected in liver, brain, spinal cord, spermatozoa,
CC muscle, white adipose tissue and brown adipose tissue (at protein
CC level). Widely expressed, except in pancreas, where expression is not
CC detectable. {ECO:0000269|PubMed:21792931, ECO:0000269|PubMed:22522610,
CC ECO:0000269|PubMed:24367518, ECO:0000269|PubMed:8603082,
CC ECO:0000269|PubMed:9725820}.
CC -!- DISRUPTION PHENOTYPE: Complete lethality during early embryonic
CC development. Heterozygous mice are viable and show no obvious
CC morphological or behavorial phenotype. Heterozygous mice that are kept
CC on a normal diet show normal weight gain, normal glucose tolerance and
CC insulin sensitivity. In contrast, mice exhibit a striking reduction in
CC weight gain relative to wild-type, when kept on a high-fat diet. This
CC is due to reduced fat accumulation in the liver and in subcutaneous
CC white adipose tissue. In addition, heterozygous mice kept on a high-fat
CC diet show higher glucose tolerance and higher insulin sensitivity than
CC wild-type. The reduced weight gain is explained by reduced food intake,
CC less efficient nutrient assimilation in the intestine and increased
CC oxygen consumption when kept on a high-fat diet. Besides, heterozygous
CC mice fail to respond to a high-fat diet by up-regulation of genes
CC involved in lipid metabolism. {ECO:0000269|PubMed:24367518}.
CC -!- MISCELLANEOUS: Overexpression in pancreatic beta-cells triggers insulin
CC secretion in response to pyruvate, causing hyperinsulemia and
CC hypoglycemia during strenuous exercise.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
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DR EMBL; X82438; CAA57819.1; -; mRNA.
DR EMBL; AF058055; AAC13720.1; -; mRNA.
DR EMBL; BC014777; AAH14777.1; -; mRNA.
DR CCDS; CCDS17702.1; -.
DR RefSeq; NP_033222.1; NM_009196.4.
DR AlphaFoldDB; P53986; -.
DR SMR; P53986; -.
DR BioGRID; 203282; 6.
DR IntAct; P53986; 2.
DR MINT; P53986; -.
DR STRING; 10090.ENSMUSP00000045216; -.
DR iPTMnet; P53986; -.
DR PhosphoSitePlus; P53986; -.
DR SwissPalm; P53986; -.
DR EPD; P53986; -.
DR jPOST; P53986; -.
DR PaxDb; P53986; -.
DR PeptideAtlas; P53986; -.
DR PRIDE; P53986; -.
DR ProteomicsDB; 291384; -.
DR Antibodypedia; 4301; 339 antibodies from 37 providers.
DR DNASU; 20501; -.
DR Ensembl; ENSMUST00000046212; ENSMUSP00000045216; ENSMUSG00000032902.
DR GeneID; 20501; -.
DR KEGG; mmu:20501; -.
DR UCSC; uc008qui.2; mouse.
DR CTD; 6566; -.
DR MGI; MGI:106013; Slc16a1.
DR VEuPathDB; HostDB:ENSMUSG00000032902; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000154955; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; P53986; -.
DR OMA; TYAGFCI; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; P53986; -.
DR TreeFam; TF313792; -.
DR Reactome; R-MMU-210991; Basigin interactions.
DR Reactome; R-MMU-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR Reactome; R-MMU-9749641; Aspirin ADME.
DR SABIO-RK; P53986; -.
DR BioGRID-ORCS; 20501; 13 hits in 73 CRISPR screens.
DR ChiTaRS; Slc16a1; mouse.
DR PRO; PR:P53986; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P53986; protein.
DR Bgee; ENSMUSG00000032902; Expressed in pigmented layer of retina and 272 other tissues.
DR ExpressionAtlas; P53986; baseline and differential.
DR Genevisible; P53986; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0046943; F:carboxylic acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0097159; F:organic cyclic compound binding; ISO:MGI.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0051780; P:behavioral response to nutrient; IMP:UniProtKB.
DR GO; GO:1905039; P:carboxylic acid transmembrane transport; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0007098; P:centrosome cycle; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0035873; P:lactate transmembrane transport; ISO:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0015718; P:monocarboxylic acid transport; ISO:MGI.
DR GO; GO:0035879; P:plasma membrane lactate transport; IMP:ARUK-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:UniProtKB.
DR GO; GO:0032094; P:response to food; IMP:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR004743; MCT.
DR InterPro; IPR030757; MCT1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11360:SF24; PTHR11360:SF24; 1.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00892; 2A0113; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Phosphoprotein; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..493
FT /note="Monocarboxylate transporter 1"
FT /id="PRO_0000211383"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..111
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..166
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..291
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 322..342
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..346
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 383..403
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 404..415
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..493
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 447..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939,
FT ECO:0007744|PubMed:18630941, ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 462
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
SQ SEQUENCE 493 AA; 53267 MW; 8B6DAB7741340DD7 CRC64;
MPPAIGGPVG YTPPDGGWGW AVLVGAFISI GFSYAFPKSI TVFFKEIEVI FSATTSEVSW
ISSIMLAVMY AGGPISSILV NKYGSRPVMI AGGCLSGCGL IAASFCNTVQ ELYLCIGVIG
GLGLAFNLNP ALTMIGKYFY KKRPLANGLA MAGSPVFLST LAPLNQAFFD IFDWRGSFLI
LGGLLLNCCV AGSLMRPIGP EQVKLEKLKS KESLQEAGKS DANTDLIGGS PKGEKLSVFQ
TINKFLDLSL FTHRGFLLYL SGNVVMFFGL FTPLVFLSSY GKSKDFSSEK SAFLLSILAF
VDMVARPSMG LAANTKWIRP RIQYFFAASV VANGVCHLLA PLSTTYVGFC VYAGVFGFAF
GWLSSVLFET LMDLIGPQRF SSAVGLVTIV ECCPVLLGPP LLGRLNDMYG DYKYTYWACG
VILIIAGIYL FIGMGINYRL LAKEQKAEEK QKREGKEDEA STDVDEKPKE TMKAAQSPQQ
HSSGDPTEEE SPV
