MOT1_RAT
ID MOT1_RAT Reviewed; 494 AA.
AC P53987;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 164.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=Wistar; TISSUE=Small intestine;
RX PubMed=8526936; DOI=10.1006/bbrc.1995.2786;
RA Takanaga H., Tamai I., Inaba S., Sai Y., Higashida H., Yamamoto H.,
RA Tsuji A.;
RT "cDNA cloning and functional characterization of rat intestinal
RT monocarboxylate transporter.";
RL Biochem. Biophys. Res. Commun. 217:370-377(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Skeletal muscle;
RX PubMed=7548134; DOI=10.1016/0005-2736(95)00160-5;
RA Jackson V.N., Price N.T., Halestrap A.P.;
RT "cDNA cloning of MCT1, a monocarboxylate transporter from rat skeletal
RT muscle.";
RL Biochim. Biophys. Acta 1238:193-196(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 264-472, FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Jejunal epithelium;
RX PubMed=10564700; DOI=10.1111/j.1469-445x.1999.01918.x;
RA Orsenigo M.N., Tosco M., Bazzini C., Laforenza U., Faelli A.;
RT "A monocarboxylate transporter MCT1 is located at the basolateral pole of
RT rat jejunum.";
RL Exp. Physiol. 84:1033-1042(1999).
RN [5]
RP INTERACTION WITH EMB, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=9169423; DOI=10.1074/jbc.272.23.14624;
RA Poole R.C., Halestrap A.P.;
RT "Interaction of the erythrocyte lactate transporter (monocarboxylate
RT transporter 1) with an integral 70-kDa membrane glycoprotein of the
RT immunoglobulin superfamily.";
RL J. Biol. Chem. 272:14624-14628(1997).
RN [6]
RP INTERACTION WITH BSG, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11719518; DOI=10.1074/jbc.m109658200;
RA Wilson M.C., Meredith D., Halestrap A.P.;
RT "Fluorescence resonance energy transfer studies on the interaction between
RT the lactate transporter MCT1 and CD147 provide information on the topology
RT and stoichiometry of the complex in situ.";
RL J. Biol. Chem. 277:3666-3672(2002).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16396499; DOI=10.1021/pr0503073;
RA Moser K., White F.M.;
RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-
RT MS/MS.";
RL J. Proteome Res. 5:98-104(2006).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BSG, TOPOLOGY,
RP 3D-STRUCTURE MODELING, AND MUTAGENESIS OF ARG-86; ARG-196; ASP-302 AND
RP ARG-306.
RX PubMed=17127621; DOI=10.1080/09687860600841967;
RA Manoharan C., Wilson M.C., Sessions R.B., Halestrap A.P.;
RT "The role of charged residues in the transmembrane helices of
RT monocarboxylate transporter 1 and its ancillary protein basigin in
RT determining plasma membrane expression and catalytic activity.";
RL Mol. Membr. Biol. 23:486-498(2006).
RN [9]
RP FUNCTION, INTERACTION WITH EMB, SUBCELLULAR LOCATION, TOPOLOGY,
RP 3D-STRUCTURE MODELING, MUTAGENESIS OF LYS-38; LYS-45; LYS-282; LYS-284;
RP LYS-290 AND LYS-413, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=19473976; DOI=10.1074/jbc.m109.014217;
RA Wilson M.C., Meredith D., Bunnun C., Sessions R.B., Halestrap A.P.;
RT "Studies on the DIDS-binding site of monocarboxylate transporter 1 suggest
RT a homology model of the open conformation and a plausible translocation
RT cycle.";
RL J. Biol. Chem. 284:20011-20021(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; SER-213; SER-220;
RP SER-230; SER-460 AND SER-492, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:10564700,
CC ECO:0000269|PubMed:11719518, ECO:0000269|PubMed:17127621,
CC ECO:0000269|PubMed:19473976, ECO:0000269|PubMed:8526936}.
CC -!- ACTIVITY REGULATION: Inhibited by stilbene disulfonates, such as di-
CC isothiocyanostilbene disulfonate(DIDS), a cross-linking reagent that
CC forms covalent linkages with lysine groups.
CC {ECO:0000269|PubMed:19473976}.
CC -!- SUBUNIT: Interacts with BSG. Interacts with EMB. Interaction with
CC either BSG or EMB is required for expression at the cell membrane.
CC {ECO:0000269|PubMed:11719518, ECO:0000269|PubMed:17127621,
CC ECO:0000269|PubMed:19473976, ECO:0000269|PubMed:9169423}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10564700,
CC ECO:0000269|PubMed:11719518, ECO:0000269|PubMed:17127621,
CC ECO:0000269|PubMed:19473976, ECO:0000269|PubMed:8526936,
CC ECO:0000269|PubMed:9169423}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10564700, ECO:0000269|PubMed:11719518,
CC ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:19473976,
CC ECO:0000269|PubMed:8526936, ECO:0000269|PubMed:9169423}.
CC -!- TISSUE SPECIFICITY: Detected in erythrocytes (at protein level).
CC Detected in brain, heart, kidney, lung, muscle, jejunum enterocytes and
CC brain capillaries. {ECO:0000269|PubMed:10564700,
CC ECO:0000269|PubMed:19473976, ECO:0000269|PubMed:8526936,
CC ECO:0000269|PubMed:9169423}.
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; D63834; BAA09894.1; -; mRNA.
DR EMBL; X86216; CAA60116.1; -; mRNA.
DR EMBL; BC078877; AAH78877.1; -; mRNA.
DR EMBL; AJ236865; CAB37948.1; -; mRNA.
DR PIR; JC4399; JC4399.
DR RefSeq; NP_036848.1; NM_012716.2.
DR RefSeq; XP_017446125.1; XM_017590636.1.
DR AlphaFoldDB; P53987; -.
DR SMR; P53987; -.
DR BioGRID; 247107; 2.
DR IntAct; P53987; 1.
DR STRING; 10116.ENSRNOP00000027234; -.
DR BindingDB; P53987; -.
DR ChEMBL; CHEMBL2073709; -.
DR iPTMnet; P53987; -.
DR PhosphoSitePlus; P53987; -.
DR jPOST; P53987; -.
DR PaxDb; P53987; -.
DR PRIDE; P53987; -.
DR Ensembl; ENSRNOT00000027234; ENSRNOP00000027234; ENSRNOG00000019996.
DR GeneID; 25027; -.
DR KEGG; rno:25027; -.
DR UCSC; RGD:3690; rat.
DR CTD; 6566; -.
DR RGD; 3690; Slc16a1.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000154955; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; P53987; -.
DR OMA; TYAGFCI; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; P53987; -.
DR TreeFam; TF313792; -.
DR Reactome; R-RNO-210991; Basigin interactions.
DR Reactome; R-RNO-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR SABIO-RK; P53987; -.
DR PRO; PR:P53987; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000019996; Expressed in heart and 19 other tissues.
DR Genevisible; P53987; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0009925; C:basal plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0046943; F:carboxylic acid transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; ISO:RGD.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0097159; F:organic cyclic compound binding; IMP:RGD.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0051780; P:behavioral response to nutrient; ISO:RGD.
DR GO; GO:1905039; P:carboxylic acid transmembrane transport; IMP:ARUK-UCL.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IMP:RGD.
DR GO; GO:0007098; P:centrosome cycle; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0035873; P:lactate transmembrane transport; IDA:RGD.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0015718; P:monocarboxylic acid transport; IDA:ARUK-UCL.
DR GO; GO:0035879; P:plasma membrane lactate transport; IDA:RGD.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
DR GO; GO:0032094; P:response to food; ISO:RGD.
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..494
FT /note="Monocarboxylate transporter 1"
FT /id="PRO_0000211384"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..59
FT /note="Extracellular"
FT /evidence="ECO:0000305"
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:0000305"
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:0000305"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..494
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 446..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16396499,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53986"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 459
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53985"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 461
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53986"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53985"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53986"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53986"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 38
FT /note="K->Q,R: No effect on expression at the cell
FT membrane, but abolishes lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
FT MUTAGEN 45
FT /note="K->Q,R: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
FT MUTAGEN 86
FT /note="R->E,Q: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:17127621"
FT MUTAGEN 196
FT /note="R->E,Q: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:17127621"
FT MUTAGEN 282
FT /note="K->Q,R: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
FT MUTAGEN 284
FT /note="K->Q,R: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
FT MUTAGEN 290
FT /note="K->Q,R: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
FT MUTAGEN 302
FT /note="D->R: Abolishes expression at the cell membrane.
FT Abolishes lactate transport across the cell membrane
FT without affecting expression at the cell membrane; when
FT associated with E-306."
FT /evidence="ECO:0000269|PubMed:17127621"
FT MUTAGEN 306
FT /note="R->E: Abolishes expression at the cell membrane.
FT Abolishes lactate transport across the cell membrane
FT without affecting expression at the cell membrane; when
FT associated with R-302."
FT /evidence="ECO:0000269|PubMed:17127621"
FT MUTAGEN 306
FT /note="R->K: No effect on expression at the cell membrane,
FT but abolishes lactate transport across the cell membrane."
FT /evidence="ECO:0000269|PubMed:17127621"
FT MUTAGEN 413
FT /note="K->Q,R: No effect on expression at the cell
FT membrane. No effect on lactate transport across the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:19473976"
SQ SEQUENCE 494 AA; 53238 MW; CF82F8794CDBF057 CRC64;
MPPAIGGPVG YTPPDGGWGW AVVVGAFISI GFSYAFPKSI TVFFKEIEII FSATTSEVSW
ISSIMLAVMY AGGPISSILV NKYGSRPVMI AGGCLSGCGL IAASFCNTVQ ELYFCIGVIG
GLGLAFNLNP ALTMIGKYFY KKRPLANGLA MAGSPVFLST LAPLNQAFFG IFGWRGSFLI
LGGLLLNCCV AGSLMRPIGP QQGKVEKLKS KESLQEAGKS DANTDLIGGS PKGEKLSVFQ
TVNKFLDLSL FTHRGFLLYL SGNVVMFFGL FTPLVFLSNY GKSKHFSSEK SAFLLSILAF
VDMVARPSMG LAANTRWIRP RVQYFFAASV VANGVCHLLA PLSTTYVGFC IYAGVFGFAF
GWLSSVLFET LMDLVGPQRF SSAVGLVTIV ECCPVLLGPP LLGRLNDMYG DYKYTYWACG
VILIIAGLYL FIGMGINYRL VAKEQKAEEK KRDGKEDETS TDVDEKPKKT MKETQSPAPL
QNSSGDPAEE ESPV
