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 27-MAR-2024, entry version 189. 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 L-lactate efflux from CC highly glycolytic cells (By similarity). {ECO:0000250|UniProtKB:O35910, CC ECO:0000269|PubMed:11101640, ECO:0000269|PubMed:23935841, CC 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="https://atlasgeneticsoncology.org/gene/44573/SLC16A3"; 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; 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; 64. DR IntAct; O15427; 35. 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; DB07767; Ferulic 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; 9606-ENSP00000463978; -. DR PeptideAtlas; O15427; -. DR ProteomicsDB; 48655; -. DR Pumba; O15427; -. DR Antibodypedia; 4302; 324 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 AGR; HGNC:10924; -. 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; YGMTEVQ; -. DR OrthoDB; 2917104at2759; -. 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; 36 hits in 1165 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 194 other cell types or tissues. DR ExpressionAtlas; O15427; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. 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:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IDA:SynGO. DR GO; GO:0015650; F:lactate:proton symporter activity; IDA:UniProtKB. DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0050833; F:pyruvate transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0035873; P:lactate transmembrane transport; IDA:UniProtKB. DR GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central. DR GO; GO:0030163; P:protein catabolic process; IDA:SynGO. DR GO; GO:0042867; P:pyruvate catabolic process; IEA:Ensembl. DR GO; GO:1901475; P:pyruvate transmembrane transport; IDA:UniProtKB. DR CDD; cd17430; MFS_MCT3_4; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR004743; MCT. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR NCBIfam; TIGR00892; 2A0113; 1. DR PANTHER; PTHR11360; MONOCARBOXYLATE TRANSPORTER; 1. DR PANTHER; PTHR11360:SF27; MONOCARBOXYLATE TRANSPORTER 4; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. DR Genevisible; O15427; HS. 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 //