MOT4_RAT
ID MOT4_RAT Reviewed; 471 AA.
AC O35910;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Monocarboxylate transporter 4;
DE Short=MCT 4;
DE AltName: Full=Monocarboxylate transporter 3 {ECO:0000303|PubMed:9632638};
DE Short=MCT 3;
DE AltName: Full=Solute carrier family 16 member 3;
GN Name=Slc16a3; Synonyms=Mct3 {ECO:0000303|PubMed:9632638}, Mct4;
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, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=Wistar; TISSUE=Skeletal muscle;
RX PubMed=9632638; DOI=10.1074/jbc.273.26.15920;
RA Wilson M.C., Jackson V.N., Heddle C., Price N.T., Pilegaard H., Juel C.,
RA Bonen A., Montgomery I., Hutter O.F., Halestrap A.P.;
RT "Lactic acid efflux from white skeletal muscle is catalyzed by the
RT monocarboxylate transporter isoform MCT3.";
RL J. Biol. Chem. 273:15920-15926(1998).
RN [2]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=10926847;
RA Dimmer K.S., Friedrich B., Lang F., Deitmer J.W., Broeer S.;
RT "The low-affinity monocarboxylate transporter MCT4 is adapted to the export
RT of lactate in highly glycolytic cells.";
RL Biochem. J. 350:219-227(2000).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [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-dependent transporter of monocarboxylates such as L-
CC lactate and pyruvate (PubMed:9632638, PubMed:10926847) (By similarity).
CC Plays a predominant role in the transport of L-lactate efflux from
CC highly glycolytic cells (PubMed:9632638, PubMed:10926847).
CC {ECO:0000250|UniProtKB:O15427, ECO:0000269|PubMed:10926847,
CC ECO:0000269|PubMed:9632638}.
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:0000269|PubMed:10926847, ECO:0000269|PubMed:9632638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29416;
CC Evidence={ECO:0000305|PubMed:10926847};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.1 mM for (S)-lactate {ECO:0000269|PubMed:9632638};
CC KM=33.7 mM for (S)-lactate {ECO:0000269|PubMed:10926847};
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:0000250|UniProtKB:O15427}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:O15427}; Multi-pass membrane
CC protein {ECO:0000255}. Note=Plasma membrane localization is dependent
CC upon the BSG/MCT4 interaction. Basolateral sorting signals (BLSS) in C-
CC terminal cytoplasmic tail ensure its basolateral expression in
CC polarised epithelial cells. {ECO:0000250|UniProtKB:O15427}.
CC -!- TISSUE SPECIFICITY: Detected in testis, small intestine, parotid gland,
CC lung and brain. Small amounts are detected in heart, kidney and spleen
CC (PubMed:10926847). Expressed in skeletal muscle (PubMed:9632638).
CC {ECO:0000269|PubMed:10926847, ECO:0000269|PubMed:9632638}.
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 -!- 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 -!- CAUTION: Was initially assigned as monocarboxylate transporter 3 (MCT3)
CC (PubMed:9632638). However, it was later shown that it corresponds to
CC monocarboxylate transporter 4 (MCT4).
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DR EMBL; U87627; AAC53591.1; -; mRNA.
DR RefSeq; NP_110461.1; NM_030834.1.
DR RefSeq; XP_006247993.1; XM_006247931.3.
DR RefSeq; XP_006247994.1; XM_006247932.2.
DR RefSeq; XP_006247995.1; XM_006247933.3.
DR RefSeq; XP_006247996.1; XM_006247934.3.
DR RefSeq; XP_008766735.1; XM_008768513.2.
DR AlphaFoldDB; O35910; -.
DR SMR; O35910; -.
DR STRING; 10116.ENSRNOP00000051822; -.
DR PaxDb; O35910; -.
DR Ensembl; ENSRNOT00000054939; ENSRNOP00000051822; ENSRNOG00000036677.
DR GeneID; 80878; -.
DR KEGG; rno:80878; -.
DR CTD; 9123; -.
DR RGD; 620603; Slc16a3.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000158181; -.
DR InParanoid; O35910; -.
DR OMA; IFARPLC; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; O35910; -.
DR Reactome; R-RNO-210991; Basigin interactions.
DR Reactome; R-RNO-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR PRO; PR:O35910; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000036677; Expressed in skeletal muscle tissue and 20 other tissues.
DR ExpressionAtlas; O35910; baseline and differential.
DR Genevisible; O35910; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
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; IDA:SynGO.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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; IDA:RGD.
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..471
FT /note="Monocarboxylate transporter 4"
FT /id="PRO_0000211396"
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..471
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 429..447
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT REGION 447..471
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P57787"
FT MOD_RES 466
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15427"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15427"
SQ SEQUENCE 471 AA; 50549 MW; 7EED86F82777527A CRC64;
MGGAVVDEGP TGIKAPDGGW GWAVLFGCFI ITGFSYAFPK AVSVFFKELM HEFGIGYSDT
AWISSILLAM LYGTGPLCSM CVNRFGCRPV MLVGGLFASL GMVAASFCRS IIQIYLTTGV
ITGLGLALNF QPSLIMLNRY FNKRRPMANG LAAAGSPVFL CALSPLGQLL QDHYGWRGGF
LILGGLLLNC CVCAALMRPL VAPQASGGAE PHGPQRPSPR LLDLSVFRDR GFLIYAVAAS
IMVLGLFVPP VFVVSYAKDM GVPDTKAAFL LTILGFIDIF ARPTAGFITG LKKVRPYSVY
LFSFAMFFNG FTDLTGSTAS DYGGLVVFCI FFGISYGMVG ALQFEVLMAI VGTQKFSSAI
GLVLLLEAVA VLIGPPSGGK LLDATKVYKY VFILAGAEVL TSSLVLLLGN FFCIGKRKRP
EVTKPEEVAS EEEKLHKPPV DVRVDSREVE HFLKAEPEKN GEVVHTPETS V
