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 14-DEC-2022, entry version 159. 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 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 2. 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 ProteomicsDB; 291386; -. DR Antibodypedia; 4302; 287 antibodies from 32 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 AGR; MGI:1933438; -. 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 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; ISS:UniProtKB. DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI. DR GO; GO:0016020; C:membrane; IBA:GO_Central. 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; ISS:UniProtKB. DR GO; GO:0015650; F:lactate:proton symporter activity; ISS:UniProtKB. DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0050833; F:pyruvate transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0035873; P:lactate transmembrane transport; ISS:UniProtKB. DR GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central. DR GO; GO:0035879; P:plasma membrane lactate transport; ISO:MGI. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:1901475; P:pyruvate transmembrane transport; ISS:UniProtKB. 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; MONOCARBOXYLATE TRANSPORTER 4; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 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 //