MOT4_MOUSE
ID MOT4_MOUSE Reviewed; 470 AA.
AC P57787; Q9ES80; Q9ESF8;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Monocarboxylate transporter 4;
DE Short=MCT 4;
DE AltName: Full=Solute carrier family 16 member 3;
GN Name=Slc16a3; Synonyms=Mct4;
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 [GENOMIC DNA / MRNA].
RC STRAIN=C3H/HeJ; TISSUE=Skeletal muscle;
RA Yoon H., Philp N.J.;
RT "Cloning and expression of mouse MCT3 and MCT4.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-430, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [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 [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=31837519; DOI=10.1016/j.isci.2019.11.041;
RA Bisetto S., Wright M.C., Nowak R.A., Lepore A.C., Khurana T.S., Loro E.,
RA Philp N.J.;
RT "New insights into the lactate shuttle: role of MCT4 in the modulation of
RT the exercise capacity.";
RL IScience 22:507-518(2019).
CC -!- FUNCTION: Proton-dependent transporter of monocarboxylates such as L-
CC lactate and pyruvate (By similarity). Plays a predominant role in the
CC transport of L-lactate efflux from highly glycolytic cells (Probable).
CC {ECO:0000250|UniProtKB:O15427, ECO:0000305|PubMed:31837519}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out);
CC Xref=Rhea:RHEA:29415, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651;
CC Evidence={ECO:0000250|UniProtKB:O15427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29416;
CC Evidence={ECO:0000250|UniProtKB:O15427};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29417;
CC Evidence={ECO:0000250|UniProtKB:O15427};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + pyruvate(out) = H(+)(in) + pyruvate(in);
CC Xref=Rhea:RHEA:64720, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:O15427};
CC -!- SUBUNIT: Interacts with BSG; interaction mediates SLC16A3 targeting to
CC the plasma membrane. {ECO:0000250|UniProtKB:O15427}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O15427};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:O15427}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Plasma membrane localization is dependent upon the
CC BSG/MCT4 interaction. Basolateral sorting signals (BLSS) in C-terminal
CC cytoplasmic tail ensure its basolateral expression in polarised
CC epithelial cells. {ECO:0000250|UniProtKB:O15427}.
CC -!- DOMAIN: Two basolateral sorting signals (BSS) in its C-terminal
CC cytoplasmic tail are required to direct SLC16A3 to the basolateral
CC membrane. {ECO:0000250|UniProtKB:O15427}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are born at normal Mendelian
CC ratio, with no apparent defects at birth. However mice exhibit impaired
CC exercise endurance with abnormal neuromuscular junctions innervation
CC and lower compound muscle action potential amplitude.
CC {ECO:0000269|PubMed:31837519}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to be considered to be a low affinity
CC lactate transporter with negligible affinity for pyruvate (By
CC similarity). However, it was later shown that SLC16A3 is a high
CC affinity lactate transporter with physiologically relevant affinity for
CC pyruvate (By similarity). {ECO:0000250|UniProtKB:O15427}.
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DR EMBL; AF178954; AAG24271.1; -; mRNA.
DR EMBL; AF204397; AAF67525.1; -; Genomic_DNA.
DR EMBL; BC046525; AAH46525.1; -; mRNA.
DR CCDS; CCDS25761.1; -.
DR RefSeq; NP_001033742.1; NM_001038653.1.
DR RefSeq; NP_001033743.1; NM_001038654.1.
DR RefSeq; NP_109621.1; NM_030696.3.
DR RefSeq; XP_011247623.1; XM_011249321.2.
DR RefSeq; XP_011247624.1; XM_011249322.2.
DR AlphaFoldDB; P57787; -.
DR SMR; P57787; -.
DR BioGRID; 219825; 1.
DR STRING; 10090.ENSMUSP00000068854; -.
DR ChEMBL; CHEMBL4802065; -.
DR iPTMnet; P57787; -.
DR PhosphoSitePlus; P57787; -.
DR SwissPalm; P57787; -.
DR EPD; P57787; -.
DR jPOST; P57787; -.
DR PaxDb; P57787; -.
DR PeptideAtlas; P57787; -.
DR PRIDE; P57787; -.
DR ProteomicsDB; 291386; -.
DR Antibodypedia; 4302; 291 antibodies from 33 providers.
DR DNASU; 80879; -.
DR Ensembl; ENSMUST00000070653; ENSMUSP00000068854; ENSMUSG00000025161.
DR Ensembl; ENSMUST00000100130; ENSMUSP00000097706; ENSMUSG00000025161.
DR Ensembl; ENSMUST00000168579; ENSMUSP00000125846; ENSMUSG00000025161.
DR GeneID; 80879; -.
DR KEGG; mmu:80879; -.
DR UCSC; uc007muw.1; mouse.
DR CTD; 9123; -.
DR MGI; MGI:1933438; Slc16a3.
DR VEuPathDB; HostDB:ENSMUSG00000025161; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000158181; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; P57787; -.
DR OMA; IFARPLC; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; P57787; -.
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 BioGRID-ORCS; 80879; 1 hit in 76 CRISPR screens.
DR PRO; PR:P57787; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P57787; protein.
DR Bgee; ENSMUSG00000025161; Expressed in hindlimb stylopod muscle and 148 other tissues.
DR ExpressionAtlas; P57787; baseline and differential.
DR Genevisible; P57787; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central.
DR GO; GO:0035879; P:plasma membrane lactate transport; ISO:MGI.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR004743; MCT.
DR InterPro; IPR030756; MCT4.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11360:SF27; PTHR11360:SF27; 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..470
FT /note="Monocarboxylate transporter 4"
FT /id="PRO_0000211395"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..61
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..179
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..267
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..321
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 322..342
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..391
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 413..470
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 429..446
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT REGION 446..470
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 465
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15427"
SQ SEQUENCE 470 AA; 50373 MW; 34E872AC1C625DE7 CRC64;
MGGAVVDEGP TGIKAPDGGW GWAVLFGCFI ITGFSYAFPK AVSVFFKELM HEFGIGYSDT
AWISSILLAM LYGTGPLCSV CVNRFGCRPV MLVGGLFASL GMVAASFCRS IIQIYLTTGV
ITGLGLALNF QPSLIMLNRY FNKRRPIANG LAAAGSPVFL CALSPLGQLL QDHYGWRGGF
LILGGLLLNC CVCAALMRPL VAPQVGGGTE PRGPQRPPQR LLDLSVFRDR GFLIYAVAAS
IMVLGLFVPP VFVVSYAKDM GVPDTKAAFL LTILGFIDIF ARPTAGFITG LKKVRPYSVY
LFSFAMFFNG FTDLTGSTAT DYGGLVVFCI FFGISYGMVG ALQFEVLMAI VGTQKFSSAI
GLVLLLEAVA VLIGPPSGGK LLDATKVYKY VFILAGAEVL TSSLVLLLGN FFCIGKRKRP
EVTEPEEVAS EEKLHKPPVD VGVDSREVEH FLKAEPEKNG EVVHTPETSV
