MOT4_HUMAN
ID MOT4_HUMAN Reviewed; 465 AA.
AC O15427; B3KXG8; Q2M1P8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Monocarboxylate transporter 4;
DE Short=MCT 4;
DE AltName: Full=Solute carrier family 16 member 3;
GN Name=SLC16A3; Synonyms=MCT3 {ECO:0000303|PubMed:9425115}, MCT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=9425115; DOI=10.1042/bj3290321;
RA Price N.T., Jackson V.N., Halestrap A.P.;
RT "Cloning and sequencing of four new mammalian monocarboxylate transporter
RT (MCT) homologues confirms the existence of a transporter family with an
RT ancient past.";
RL Biochem. J. 329:321-328(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 PROTEIN SEQUENCE OF 2-14 AND 429-441, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Lao L., Ryan K.L.;
RL Submitted (OCT-2009) to UniProtKB.
RN [5]
RP INTERACTION WITH BSG, AND SUBCELLULAR LOCATION.
RX PubMed=10921872; DOI=10.1093/emboj/19.15.3896;
RA Kirk P., Wilson M.C., Heddle C., Brown M.H., Barclay A.N., Halestrap A.P.;
RT "CD147 is tightly associated with lactate transporters MCT1 and MCT4 and
RT facilitates their cell surface expression.";
RL EMBO J. 19:3896-3904(2000).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11101640; DOI=10.1111/j.1469-7793.2000.00285.x;
RA Manning Fox J.E., Meredith D., Halestrap A.P.;
RT "Characterisation of human monocarboxylate transporter 4 substantiates its
RT role in lactic acid efflux from skeletal muscle.";
RL J. Physiol. (Lond.) 529:285-293(2000).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=15505343; DOI=10.1369/jhc.4a6306.2004;
RA Merezhinskaya N., Ogunwuyi S.A., Mullick F.G., Fishbein W.N.;
RT "Presence and localization of three lactic acid transporters (MCT1, -2, and
RT -4) in separated human granulocytes, lymphocytes, and monocytes.";
RL J. Histochem. Cytochem. 52:1483-1493(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP INDUCTION.
RX PubMed=16452478; DOI=10.1074/jbc.m511397200;
RA Ullah M.S., Davies A.J., Halestrap A.P.;
RT "The plasma membrane lactate transporter MCT4, but not MCT1, is up-
RT regulated by hypoxia through a HIF-1alpha-dependent mechanism.";
RL J. Biol. Chem. 281:9030-9037(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460 AND SER-464, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460 AND SER-464, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-425; GLU-426; GLU-427; PRO-432
RP AND PRO-433.
RX PubMed=21199217; DOI=10.1111/j.1600-0854.2010.01155.x;
RA Castorino J.J., Deborde S., Deora A., Schreiner R., Gallagher-Colombo S.M.,
RA Rodriguez-Boulan E., Philp N.J.;
RT "Basolateral sorting signals regulating tissue-specific polarity of
RT heteromeric monocarboxylate transporters in epithelia.";
RL Traffic 12:483-498(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ARG-198 AND ARG-278.
RX PubMed=23935841; DOI=10.1371/journal.pone.0067690;
RA Sasaki S., Kobayashi M., Futagi Y., Ogura J., Yamaguchi H., Takahashi N.,
RA Iseki K.;
RT "Crucial residue involved in L-lactate recognition by human monocarboxylate
RT transporter 4 (hMCT4).";
RL PLoS ONE 8:e67690-e67690(2013).
RN [17]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP TRANSPORTER ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=31719150; DOI=10.1074/jbc.ra119.009093;
RA Contreras-Baeza Y., Sandoval P.Y., Alarcon R., Galaz A., Cortes-Molina F.,
RA Alegria K., Baeza-Lehnert F., Arce-Molina R., Guequen A., Flores C.A.,
RA San Martin A., Barros L.F.;
RT "Monocarboxylate transporter 4 (MCT4) is a high affinity transporter
RT capable of exporting lactate in high-lactate microenvironments.";
RL J. Biol. Chem. 294:20135-20147(2019).
CC -!- FUNCTION: Proton-dependent transporter of monocarboxylates such as L-
CC lactate and pyruvate (PubMed:11101640, PubMed:23935841,
CC PubMed:31719150). Plays a predominant role in the transport of L-
CC lactate efflux from highly glycolytic cells (By similarity).
CC {ECO:0000250|UniProtKB:O35910, ECO:0000269|PubMed:11101640,
CC ECO:0000269|PubMed:23935841, ECO:0000269|PubMed:31719150}.
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:11101640, ECO:0000269|PubMed:23935841,
CC ECO:0000269|PubMed:31719150};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29416;
CC Evidence={ECO:0000269|PubMed:31719150};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29417;
CC Evidence={ECO:0000269|PubMed:31719150};
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:0000269|PubMed:31719150};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.4 mM for (S)-lactate (pH 5.5) {ECO:0000269|PubMed:23935841};
CC KM=37.6 mM for (S)-lactate (pH 7.5) {ECO:0000269|PubMed:23935841};
CC KM=28 mM for (S)-lactate {ECO:0000269|PubMed:11101640};
CC KM=519 mM for D-lactate {ECO:0000269|PubMed:11101640};
CC KM=153 mM for pyruvate {ECO:0000269|PubMed:11101640};
CC KM=1.7 mM for (S)-lactate {ECO:0000269|PubMed:31719150};
CC KM=4.2 mM for pyruvate {ECO:0000269|PubMed:31719150};
CC -!- SUBUNIT: Interacts with BSG; interaction mediates SLC16A3 targeting to
CC the plasma membrane. {ECO:0000269|PubMed:10921872}.
CC -!- INTERACTION:
CC O15427; Q8N9N5: BANP; NbExp=3; IntAct=EBI-7600166, EBI-744695;
CC O15427; Q12959: DLG1; NbExp=2; IntAct=EBI-7600166, EBI-357481;
CC O15427; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-7600166, EBI-10175124;
CC O15427; P48165: GJA8; NbExp=3; IntAct=EBI-7600166, EBI-17458373;
CC O15427; Q8WUI4-6: HDAC7; NbExp=3; IntAct=EBI-7600166, EBI-12094670;
CC O15427; P84074: HPCA; NbExp=5; IntAct=EBI-7600166, EBI-12197079;
CC O15427; Q86WQ0: NR2C2AP; NbExp=3; IntAct=EBI-7600166, EBI-10260040;
CC O15427; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-7600166, EBI-741480;
CC O15427; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-7600166, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10921872,
CC ECO:0000269|PubMed:11101640, ECO:0000269|PubMed:15505343,
CC ECO:0000269|PubMed:23935841}; Multi-pass membrane protein. Basolateral
CC cell membrane {ECO:0000269|PubMed:21199217}; Multi-pass membrane
CC protein {ECO:0000255}. Note=Plasma membrane localization is dependent
CC upon the BSG/MCT4 interaction (PubMed:10921872). Basolateral sorting
CC signals (BLSS) in C-terminal cytoplasmic tail ensure its basolateral
CC expression in polarised epithelial cells (PubMed:21199217).
CC {ECO:0000269|PubMed:10921872, ECO:0000269|PubMed:21199217}.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle.
CC {ECO:0000269|PubMed:9425115}.
CC -!- INDUCTION: Up-regulated by hypoxia through a HIF1A-mediated mechanism.
CC {ECO:0000269|PubMed:16452478}.
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:0000269|PubMed:21199217}.
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
CC (PubMed:11101640). However, it was later shown that SLC16A3 is a high
CC affinity lactate transporter with physiologically relevant affinity for
CC pyruvate (PubMed:31719150). {ECO:0000269|PubMed:11101640,
CC ECO:0000269|PubMed:31719150}.
CC -!- CAUTION: Was initially assigned as monocarboxylate transporter 3 (MCT3)
CC (PubMed:9425115). However, it was later shown that it corresponds to
CC monocarboxylate transporter 4 (MCT4). {ECO:0000305|PubMed:9425115}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SLC16A3ID44573ch17q25.html";
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DR EMBL; U81800; AAC52015.1; -; mRNA.
DR EMBL; AK127319; BAG54480.1; -; mRNA.
DR EMBL; BC112267; AAI12268.1; -; mRNA.
DR EMBL; BC112269; AAI12270.1; -; mRNA.
DR CCDS; CCDS11804.1; -.
DR RefSeq; NP_001035887.1; NM_001042422.2.
DR RefSeq; NP_001035888.1; NM_001042423.2.
DR RefSeq; NP_001193879.1; NM_001206950.1.
DR RefSeq; NP_001193880.1; NM_001206951.1.
DR RefSeq; NP_001193881.1; NM_001206952.1.
DR RefSeq; NP_004198.1; NM_004207.3.
DR RefSeq; XP_011521909.1; XM_011523607.1.
DR AlphaFoldDB; O15427; -.
DR SMR; O15427; -.
DR BioGRID; 114571; 54.
DR IntAct; O15427; 33.
DR MINT; O15427; -.
DR STRING; 9606.ENSP00000463978; -.
DR BindingDB; O15427; -.
DR ChEMBL; CHEMBL2073663; -.
DR DrugBank; DB01762; Acetoacetic acid.
DR DrugBank; DB04074; alpha-Ketoisovalerate.
DR DrugBank; DB03066; D-Lactic acid.
DR DrugBank; DB01942; Formic acid.
DR DrugBank; DB01440; gamma-Hydroxybutyric acid.
DR DrugBank; DB04343; Glyoxylic acid.
DR DrugBank; DB04398; Lactic acid.
DR DrugBank; DB00627; Niacin.
DR DrugBank; DB03940; Oxamic Acid.
DR DrugBank; DB03884; Phenylpyruvic acid.
DR DrugBank; DB00119; Pyruvic acid.
DR GuidetoPHARMACOLOGY; 989; -.
DR TCDB; 2.A.1.13.6; the major facilitator superfamily (mfs).
DR GlyGen; O15427; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15427; -.
DR PhosphoSitePlus; O15427; -.
DR SwissPalm; O15427; -.
DR BioMuta; SLC16A3; -.
DR EPD; O15427; -.
DR jPOST; O15427; -.
DR MassIVE; O15427; -.
DR MaxQB; O15427; -.
DR PaxDb; O15427; -.
DR PeptideAtlas; O15427; -.
DR PRIDE; O15427; -.
DR ProteomicsDB; 48655; -.
DR Antibodypedia; 4302; 291 antibodies from 33 providers.
DR DNASU; 9123; -.
DR Ensembl; ENST00000392339.6; ENSP00000376150.1; ENSG00000141526.18.
DR Ensembl; ENST00000392341.6; ENSP00000376152.1; ENSG00000141526.18.
DR Ensembl; ENST00000580189.6; ENSP00000464112.2; ENSG00000141526.18.
DR Ensembl; ENST00000581287.5; ENSP00000463978.1; ENSG00000141526.18.
DR Ensembl; ENST00000582743.6; ENSP00000462405.1; ENSG00000141526.18.
DR Ensembl; ENST00000584689.6; ENSP00000464625.2; ENSG00000141526.18.
DR Ensembl; ENST00000617373.5; ENSP00000483212.1; ENSG00000141526.18.
DR Ensembl; ENST00000619321.2; ENSP00000482013.1; ENSG00000141526.18.
DR GeneID; 9123; -.
DR KEGG; hsa:9123; -.
DR MANE-Select; ENST00000582743.6; ENSP00000462405.1; NM_004207.4; NP_004198.1.
DR UCSC; uc002keb.4; human.
DR CTD; 9123; -.
DR DisGeNET; 9123; -.
DR GeneCards; SLC16A3; -.
DR HGNC; HGNC:10924; SLC16A3.
DR HPA; ENSG00000141526; Tissue enhanced (skeletal).
DR MIM; 603877; gene.
DR neXtProt; NX_O15427; -.
DR OpenTargets; ENSG00000141526; -.
DR PharmGKB; PA35815; -.
DR VEuPathDB; HostDB:ENSG00000141526; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000158181; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; O15427; -.
DR OMA; IFARPLC; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; O15427; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; O15427; -.
DR Reactome; R-HSA-210991; Basigin interactions.
DR Reactome; R-HSA-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-HSA-70268; Pyruvate metabolism.
DR SignaLink; O15427; -.
DR SIGNOR; O15427; -.
DR BioGRID-ORCS; 9123; 35 hits in 1085 CRISPR screens.
DR ChiTaRS; SLC16A3; human.
DR GeneWiki; SLC16A3; -.
DR GenomeRNAi; 9123; -.
DR Pharos; O15427; Tchem.
DR PRO; PR:O15427; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O15427; protein.
DR Bgee; ENSG00000141526; Expressed in stromal cell of endometrium and 192 other tissues.
DR ExpressionAtlas; O15427; baseline and differential.
DR Genevisible; O15427; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
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; IEA:Ensembl.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
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:0003723; F:RNA binding; HDA:UniProtKB.
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; IEA:Ensembl.
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; Direct protein sequencing; Membrane; Phosphoprotein;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:25944712"
FT CHAIN 2..465
FT /note="Monocarboxylate transporter 4"
FT /id="PRO_0000211394"
FT TOPO_DOM 2..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..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..294
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..317
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..384
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..465
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 419..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..441
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000269|PubMed:21199217"
FT REGION 441..465
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000269|PubMed:21199217"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 460
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MUTAGEN 198
FT /note="R->Q: Does not affect lactate transmembrane
FT transporter activity."
FT /evidence="ECO:0000269|PubMed:23935841"
FT MUTAGEN 278
FT /note="R->Q,K: Abolishes lactate transmembrane transporter
FT activity. Does not affect cell membrane localization."
FT /evidence="ECO:0000269|PubMed:23935841"
FT MUTAGEN 425
FT /note="E->A: Affects subcellular localization leading to
FT apical localization. Affects subcellular localization
FT leading to apical localization; when associated with A-426
FT and A-427."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 426
FT /note="E->A: Leads to a nonpolar expression pattern.
FT Affects subcellular localization leading to apical
FT localization; when associated with A-425 and A-427."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 427
FT /note="E->A: Affects subcellular localization leading to
FT apical localization. Affects subcellular localization
FT leading to apical localization; when associated with A-425
FT and A-426."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 432
FT /note="P->A: Does not affect basolateral plasma membrane
FT localization. Intracellular accumulation. Affects
FT subcellular localization leading to apical localization;
FT when associated with A-433."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 433
FT /note="P->A: Does not affect basolateral plasma membrane
FT localization. Intracellular accumulation. Affects
FT subcellular localization leading to apical localization;
FT when associated with A-432."
FT /evidence="ECO:0000269|PubMed:21199217"
SQ SEQUENCE 465 AA; 49469 MW; 7BF6384B0F14D927 CRC64;
MGGAVVDEGP TGVKAPDGGW GWAVLFGCFV ITGFSYAFPK AVSVFFKELI QEFGIGYSDT
AWISSILLAM LYGTGPLCSV CVNRFGCRPV MLVGGLFASL GMVAASFCRS IIQVYLTTGV
ITGLGLALNF QPSLIMLNRY FSKRRPMANG LAAAGSPVFL CALSPLGQLL QDRYGWRGGF
LILGGLLLNC CVCAALMRPL VVTAQPGSGP PRPSRRLLDL SVFRDRGFVL YAVAASVMVL
GLFVPPVFVV SYAKDLGVPD TKAAFLLTIL GFIDIFARPA AGFVAGLGKV RPYSVYLFSF
SMFFNGLADL AGSTAGDYGG LVVFCIFFGI SYGMVGALQF EVLMAIVGTH KFSSAIGLVL
LMEAVAVLVG PPSGGKLLDA THVYMYVFIL AGAEVLTSSL ILLLGNFFCI RKKPKEPQPE
VAAAEEEKLH KPPADSGVDL REVEHFLKAE PEKNGEVVHT PETSV
